Background
Methods
Trial type
Participants
Interventions
Outcome measures
Data collection
Assessment of risk of bias
Statistical analysis
Results
Literature search and trial characteristics
Search results
Trial characteristics
Study | Kidney disease | No. of patients included | Intervention group | Control group | Co-intervention | Study duration | Baseline eGFR (ml/min/1.73 m2) | Endpoints |
---|---|---|---|---|---|---|---|---|
Abolghasmi 2011 [24] | CKD with resistant hypertension | 41 | Spironolactone 25–50 mg | Placebo | multi-drug regime including ACE-I+/−ARB | 12 weeks | Not available | BP, potassium, creatinine, urinary sodium |
Ando 2014 [28] | CKD with hypertension | 314 | Eplerenone 50 mg | Placebo | ACE-I+/−ARB of at least 8 weeks duration | 1 year | Treatment 67.7 ± 14.3 Control 68.6 ± 13.6 | UACR, creatinine, eGFR, urinary L-FABP, 24 h urinary sodium, incidence of cerebrovascular and cardiovascular events |
Bianchi 2006 [36] | Non-diabetic CKD (idiopathic GN) | 165 | Spironolactone 25 mg | ACE-I+/−ARB | ACE-I+/−ARB | 1 year | Treatment 62.4 ± 21.9 Control 62.2 ± 19.0 | 24 h urinary protein, BP, creatinine, eGFR potassium |
Boesby 2011 [29] (XO) | Non-diabetic CKD | 40 | Eplerenone 25–50 mg | multi-drug regime including ACE-I+/−ARB | multi-drug regime including ACE-I+/−ARB | 8 weeks | 59 ± 26 | 24 h urinary albumin, BP, potassium, creatinine clearance |
Boesby 2013 [30] | Diabetic and non-diabetic CKD | 26 | Eplerenone 25–50 mg | ACE-I+/−ARB | ACE-I+/−ARB | 24 weeks | 36 ± 10 | cfPWV, AIx, AASI, 24 h urinary albumin |
Chrysostomou 2006a [37] | Diabetic and non-diabetic CKD | 41 | Spironolactone 25 mg | Placebo as ARB; Placebo as Spironolactone | ACE-I alone; ACE-I + ARB | 3 months | Not available | 24 h urinary protein, BP, creatinine, creatinine clearance, potassium |
Edwards 2009 [23] | Non-diabetic CKD with no renovascular diagnosis | 112 | Spironolactone 25 mg | Placebo | ACE-I/ARB | 36 weeks | Treatment 49 ± 12 Control 53 ± 11 | LVMI, cfPWV, aortic distensibility, AIx, BP |
Epstein 2006+ [38] | Diabetic nephropathy | 359 | Eplerenone 50 mg or 100 mg | Placebo | ACE-I | 12 weeks | ACE ± EPL 50 73 (62.1–83.6) ACE ± EPL 100 75 (62.8–85.9) Control 74 (60.5–82.2) | UACR, potassium, BP, eGFR |
Guney 2009 [25] | Non-diabetic CKD | 24 | Spironolactone 25 mg | ACE-I+/−ARB | ACE-I+/−ARB | 6 months | Treatment 63.0 ± 22.71 Control 56.3 ± 35.6 | UPCR, urinary TGF-β1, eGFR, creatinine, potassium, BP, aldosterone |
Mehdi 2009 [22] | Diabetic nephropathy | 81 | Spironolactone 25 mg | Placebo or ARB | ACE-I | 48 weeks | Not available | UACR, BP, creatinine clearance, potassium |
Nielsen 2012 [26] (XO) | Diabetes with microalbuminuria | 21 | Spironolactone 25 mg | Placebo | ACE-I/ARB | 60 days | Not available | 24 h urinary albumin, BP, GFR, urinary L-FABP, urinary NGAL, urinary KIM-1 |
Rossing 2005 [39] (XO) | Diabetic nephropathy | 20 | Spironolactone 25 mg | Placebo | ACE-I+/−ARB | 8 weeks | Not available | 24 h urinary albumin, BP, GFR |
Saklayen 2008 [43] (XO) | Diabetic nephropathy | 24 | Spironolactone 25–50 mg | Placebo | ACE-I/ARB | 3 months | Treatment 61.9 ± 23.4 Control 54.4 ± 20.1 | BP, creatinine, potassium, UPCR |
Schjoedt 2005 [40] (XO) | Diabetic nephropathy | 20 | Spironolactone 25 mg | Placebo | ACE-I+/−ARB | 2 months | Not available | 24 h urinary albumin, BP, GFR |
Tylicki 2008 [41] (XO) | Non-diabetic CKD | 18 | Spironolactone 25 mg | ACE-I + ARB | ACE-I + ARB | 8 weeks | 107.8 (93–140.9) | 24 h urinary protein, BP, creatinine, potassium, PRA, urinary NAG, urinary PIIINP |
Tylicki 2012 [31] (XO) | Non-diabetic CKD | 18 | Eplerenone 50 mg | ARB + Aliskiren | ARB | 8 weeks | Not available | UACR, BP, creatinine clearance, potassium |
van den Meiracker 2006 [42] | Diabetic nephropathy | 53 | Spironolactone 25–50 mg | Placebo | ACE-I/ARB | 1 year | Treatment 93.1 ± 45 Control 66.3 ± 35.1 | 24 h urinary protein, BP, creatinine, eGFR, potassium |
Wang 2013 [34] | Diabetic and non-diabetic CKD | 208 | Spironolactone 20 mg | multi-drug regime including ACE-I+/−ARB | multi-drug regime including ACE-I+/−ARB | 16 weeks | Treatment 65.8 ± 22.2 Control 66.5 ± 24.3 | 24 h urinary protein, creatinine, potassium, eGFR, BP, aldosterone |
Ziaee 2013 [27] | Diabetes with microalbuminuria | 60 | Spironolactone 25 mg | ACE-I | ACE-I | 12 weeks | Treatment 79.8 ± 18 Control 82.5 ± 19.1 | UACR, BP, potassium, eGFR |
Trial quality
Trial outcomes
Effect of treatment on blood pressure
Variable | Measurement | No. of study groups | No. patients in intervention | No. patients in placebo/control | Effect size (95 % CI) | I2 (p value) |
---|---|---|---|---|---|---|
Systolic BP (mmHg) | Change from baseline | 9 | 260 | 266 | −3.30 (−5.56, −1.04) | 40.0 % (0.101) |
Final visit | 16 | 666 | 659 | −5.69 (−9.04, −2.34) | 81.8 % (0.000) | |
Diastolic BP (mmHg) | Change from baseline | 9 | 260 | 266 | −2.84 (−3.35, −2.33) | 0.0 % (0.799) |
Final visit | 16 | 666 | 659 | −1.73 (−3.37, −0.10) | 68.3 % (0.000) |
Effect of treatment on renal excretory function
Variable | Measurement | No. of study groups | No. patients in intervention | No. patients in placebo/control | Effect size (95 % CI) | I2 (p value) |
---|---|---|---|---|---|---|
Creatinine (μmol/L) | Final visit | 16 | 601 | 595 | 3.83 (−2.14, 9.79) | 50.4 % (0.011) |
Creatinine Clearance (ml/min) | Final visit | 6 | 132 | 130 | −2.51 (−7.05, 2.04) | 0.0 % (0.599) |
eGFR (ml/min/1.73 m2) | Final visit | 13 | 626 | 617 | −2.71 (−4.85, −0.57) | 0.0 % (0.727) |
GFR (any measure) | Final visit | 17 | 692 | 682 | −3.15 (−5.36, −0.95) | 0.0 % (0.790) |
Urinary ACR (mg/mmol) | Final visit | 7 | 355 | 351 | −10.91 (−26.15, 4.32) | 83.4 % (0.000) |
Urinary PCR (g/g creatinine) | Final visit | 4 | 146 | 150 | −0.91 (−1.35, −0.46) | 58.4 % (0.065) |
24 h urinary albumin excretion (mg/24 h) | Final visit | 6 | 151 | 155 | −332.91 (−624.80, −41.02) | 66.5 % (0.011) |
Change from baseline | 3 | 90 | 94 | −292.23 (−422.19, −162.27) | 0.0 % (0.606) | |
24 h urinary protein excretion (g/24 h) | Final visit | 2 | 124 | 121 | −0.41 (−0.90, 0.09) | 77.1 % (0.037) |